Rituximab, Cladribine, and Temsirolimus in Treating Patients With Newly Diagnosed Mantle Cell Lymphoma

Lymphoma Clinical Trial

Official title:

Phase I/II Trial of Rituximab, Cladribine, and Temsirolimus (RCT) Therapy in Newly Diagnosed Mantle Cell Lymphoma (MCL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00787969
• Other study ID #: NCCTG-N078D
• Secondary ID: NCI-2009-00669CD
• Status: Completed
• Phase: Phase 1
• First received: November 7, 2008
• Last updated: January 8, 2018
• Start date: April 2009
• Est. completion date: June 15, 2017

Study information

• Verified date: January 2018
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase I/II trial studies the side effects and best dose of temsirolimus when given together with cladribine and rituximab and to see how well it works in treating patients with newly diagnosed mantle cell lymphoma. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cladribine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving temsirolimus together with cladribine and rituximab may kill more cancer cells.

Description:

PRIMARY OBJECTIVES:

I. To assess the efficacy and safety of the combination of rituximab, cladribine, and temsirolimus for newly diagnosed mantle cell lymphoma.

II. To determine the maximum tolerated dose (MTD) of temsirolimus combined with a fixed dose and schedule of rituximab and cladribine. (Phase I) III. To assess the efficacy of the combination of rituximab, cladribine, and temsirolimus for newly diagnosed mantle cell lymphoma with the proportion of complete responses as the primary endpoint. (Phase II)

SECONDARY OBJECTIVES:

I. To assess other measures of efficacy of the regimen including progression free survival, duration of response, and overall survival.

II. To assess the toxicity profile of the combination of rituximab, cladribine, and temsirolimus.

III. To assess efficacy using traditional lymphoma parameters and absolute lymphocyte count.

IV. To assess metabolic markers (hyperglycemia, hyperlipidemia) as markers of mammalian target of rapamycin (mTOR) inhibition using the glucose and lipid measurements being performed in the clinical laboratory as part of routine care.

V. To correlate response with serum free light chains, single nucleotide polymorphisms (SNPs) in host immune genes, vitamin D metabolites, and phosphatidylinositide 3-kinase (PI3K) pathway member expression.

VI. As part of ongoing research for North Central Cancer Treatment Group (NCCTG) lymphoma studies, paraffin-embedded tissue blocks/slides and blood products will be banked for future studies.

OUTLINE: This is a phase I, dose-escalation study of temsirolimus followed by a phase II study.

Patients receive rituximab intravenously (IV) on day 1 and cladribine IV over 2 hours on days 1-5. Patients then receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive filgrastim subcutaneously (SC) on days 6-15 or pegfilgrastim SC on day 6. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 4 months for 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: June 15, 2017
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed mantle cell lymphoma (MCL); the diagnosis must be confirmed by NCCTG pre-registration pathology review by Dr. Paul Kurtin or his designate; it is recommended that the biopsy be an excisional biopsy, but adequate core-needle biopsies will be accepted as long as they are considered adequate for registration by Dr. Kurtin or his designate; the tumor must be cyclin D-1 positive by immunohistochemistry or have evidence of a t(11;14) translocation by fluorescence based in situ hybridization (FISH) or cytogenetics

• Measurable or assessable disease, defined as at least one of the following:

• A lymph node or tumor mass that is >= 2.0 cm in at least one dimension by positron emission tomography (PET)/computed tomography (CT), CT, magnetic resonance imaging (MRI), or plain radiograph imaging

• Splenic enlargement may be used as a measurable parameter if the spleen is palpable >= 3 cm below the left costal margin

• Diffuse infiltration of an organ such as the stomach, bone marrow, peripheral blood, liver, lungs, or bowel by lymphoma without a discrete mass would constitute assessable, but not measurable, disease

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, 2, or 3

• Life expectancy >= 12 weeks

• Absolute neutrophil count (ANC) >= 1,500/mm³

• Platelet count (PLT) >= 100,000/mm³

• Serum creatinine =< 2.0 mg/dL

• Serum total bilirubin (or direct bilirubin if total is abnormal) =< institutional upper limit of normal (ULN) with or without secondary liver involvement

• Serum glutamic oxaloacetic transaminase (SGOT) =< 3 x institutional ULN (exception: if there is liver involvement, SGOT must be =< 5 x institutional ULN)

• Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only

• Willingness to return to NCCTG enrolling institution for follow-up

• Willingness to provide the blood specimens as required by the protocol

• Willingness to provide tissue specimens as required by the protocol

• Willing to return to NCCTG enrolling institution for follow-up

• Willing to provide blood and tissue specimens as required by the protocol

• Willing to abstain from eating grapefruit or drinking grapefruit juice

• Willingness to abstain from eating grapefruit or drinking grapefruit juice for the duration of the study

Exclusion Criteria

• Any prior therapy for mantle cell non-Hodgkin lymphoma including radiation therapy; exception: patient may have undergone a splenectomy for diagnosis, cytopenia, or systematic splenomegaly

• Active or uncontrolled infection

• Any of the following cardiac conditions:

• Uncontrolled high blood pressure

• Unstable angina

• Active congestive heart failure

• Myocardial infarction =< 6 months

• Serious uncontrolled cardiac arrhythmia

• Known central nervous system (CNS) involvement

• Any of the following:

• Pregnant women or women of reproductive ability who are unwilling to use effective contraception while taking the drug and for 12 months after stopping treatment

• Nursing women

• Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 12 months after stopping treatment

• Medical or psychiatric conditions which, in the opinion of the investigator, make the patient a poor risk for participation

• Known to be human immunodeficiency virus (HIV) positive; HIV testing is not required but should be done if clinically indicated; HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study

• Concurrent malignancy =< 5 years ago; exceptions: carcinoma in situ of the cervix, resected basal cell or squamous cell carcinomas of the skin, or prostate cancer that is in remission following a radical retropubic prostatectomy or radiation therapy; if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer

• Known hypersensitivity to rituximab or its components, or to murine proteins

• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

• Prior treatment with an mTOR inhibitor

• Autologous or allogeneic stem cell transplant planned as part of initial therapy

• Receiving enzyme-inducing antiepileptic drugs (enzyme inducing anti-epileptic drugs [EIAEDs]; e.g., phenytoin, fosphenytoin, carbamazepine, oxcarbazepine, phenobarbital, or primidone); any other potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer such as rifampin, glucocorticoids at greater than adrenal replacement levels, or St. John's wort; or receiving strong CYP3A4 inhibitors * Note: if these agents are discontinued, temsirolimus therapy can begin >= 7 days after discontinuation of such agent

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell

Intervention

Biological:
• rituximab
Give IV

Drug:
• cladribine
Give IV
• temsirolimus
Give IV

Biological:
• Filgrastim
Give SC
• Pegfilgrastim

Locations

Country	Name	City	State
United States	McFarland Clinic, PC	Ames	Iowa
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	Mecosta County Medical Center	Big Rapids	Michigan
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Bismarck Cancer Center	Bismarck	North Dakota
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	Illinois CancerCare - Bloomington	Bloomington	Illinois
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Graham Hospital	Canton	Illinois
United States	Illinois CancerCare - Canton	Canton	Illinois
United States	Illinois CancerCare - Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	CCOP - Duluth	Duluth	Minnesota
United States	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota
United States	Miller - Dwan Medical Center	Duluth	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Elkhart Clinic, LLC	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Michiana Hematology-Oncology, PC - Elkhart	Elkhart	Indiana
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	Eureka Community Hospital	Eureka	Illinois
United States	Illinois CancerCare - Eureka	Eureka	Illinois
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Illinois CancerCare - Galesburg	Galesburg	Illinois
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Illinois CancerCare - Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Northern Montana Hospital	Havre	Montana
United States	St. Peter's Hospital	Helena	Montana
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Howard Community Hospital	Kokomo	Indiana
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas
United States	Illinois CancerCare - Macomb	Macomb	Illinois
United States	McDonough District Hospital	Macomb	Illinois
United States	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Michiana Hematology-Oncology, PC - South Bend	Mishawaka	Indiana
United States	Saint Joseph Regional Medical Center	Mishawaka	Indiana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Illinois CancerCare - Monmouth	Monmouth	Illinois
United States	OSF Holy Family Medical Center	Monmouth	Illinois
United States	Mercy General Health Partners	Muskegon	Michigan
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Michiana Hematology Oncology PC - Niles	Niles	Michigan
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Illinois CancerCare - Community Cancer Center	Normal	Illinois
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare - Pekin	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare - Peru	Peru	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Michiana Hematology Oncology PC - Plymouth	Plymouth	Indiana
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Illinois CancerCare - Princeton	Princeton	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan
United States	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	St. Nicholas Hospital	Sheboygan	Wisconsin
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Illinois CancerCare - Spring Valley	Spring Valley	Illinois
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Munson Medical Center	Traverse City	Michigan
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Michiana Hematology Oncology PC - La Porte	Westville	Indiana
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota
United States	Metro Health Hospital	Wyoming	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of dose limiting toxicity incidents as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 3.0 (Phase I)		28 days
Primary	Proportion of complete tumor responses defined as complete remission (CR) as the objective status (Phase II)		Up to 5 years
Secondary	Overall survival		up to 5 years
Secondary	Progression-free survival (PFS)		up to 5 years
Secondary	Time to disease progression		up to 5 years
Secondary	Duration of response, defined as date at which the patient's objective status is first noted to be either a CR or partial remission to the date progression is documented		Up to 5 years
Secondary	Survival time		Up to 5 years
Secondary	Frequency and severity of adverse events assessed by CTCAE v3.0		Up to 5 years